The University of Minnesota (UMN) Udall Center will focus on understanding the electrophysiological features that underlie the motor signs of Parkinson's disease (PD) and developing new deep brain stimulation (DBS) strategies to treat them. This will be accomplished in humans through a combination of intra-operative microelectrode and post-operative local field potential (LFP) recordings using the Medtronic RC+S ?Brain Radio?, and DBS therapy implemented through the lens of novel targets and stimulation paradigms. These data will be complemented in nonhuman primates, by the development and electrophysiological characterization of optimization tools for improving subject-specific precision of DBS therapy. Specifically, the first goal (Project 1) is to enhance our understanding of the pathophysiological basis of PD motor signs by clarifying the changes in synchronized oscillatory activity that occur within the pallidum and STN at rest and during movement under conditions that improve and worsen motor signs (during DBS or following administration of levo-dopa). These data will provide the rationale for the development of novel DBS paradigms and targets. The second goal (Project 2) is to identify the physiological signatures associated with dopa-responsive and resistant motor features of PD, use MRI-derived computational models to examine the pathways mediating the behavioral changes and investigate alternative DBS targets and stimulation paradigms to treat these motor signs. The third goal (Project 3) is to leverage the well-established MPTP nonhuman primate model of PD to identify unconventional DBS settings that increase the window between successful therapy and emergence of side effects, develop closed-loop strategies for tuning DBS settings to maximize the therapeutic effect on individual parkinsonian motor signs, and investigate how the level of therapy depends on electrophysiological changes in the basal ganglia, thalamus, and brainstem. Critical to all three projects is the ability to accurately determine DBS lead and contact locations, and develop model based predictions of which motor pathways are activated during stimulation (Imaging Core). Clinical and quantitative motor assessments will be obtained (Clinical Core) and correlated to physiological data obtained acutely in the operating room, subacutely in patients whose leads are externalized and chronically through postoperative assessments using the Medtronic RC+S ?Brain Radio?. The Biostatistics Core will provide study design, logistics planning, overall data management, quality control and statistical analysis, as well as data integration with and transfer to the NIH/NINDS Data Management Resource. The Administrative Core will support all aspects of the UMN Udall Center, implement and support patient education and public outreach efforts and provide training for the next generation of PD researchers. Together, these approaches will provide critical data towards the development and translation of novel patient-specific DBS therapies.